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OBJECTIVE: The objective of this study was to provide a national health and disability profile of Canadian school-aged children based on the World Health Organization's definitions of health condition and disability that would facilitate international comparisons of child health data. METHODS: Data were used from the National Longitudinal Survey of Children and Youth, a 1994 - 95 population-based sample of 22 831 children. FINDINGS: An estimated total of 30.3% of Canadian children aged 6 to 11 had one or more chronic physical health conditions/impairments, while 3.6% had activity-limiting conditions/impairments. Children living with one parent were significantly more likely to have activity-limiting conditions/impairments than those living with two parents. Children with conditions/impairments, particularly those with activity limitations, were significantly more likely than children without health problems to have experienced mental health conditions and learning disabilities, missed school days, received special education, visited health professionals, been hospitalized, and used prescription medication. CONCLUSION: Important differences were found among children in a number of areas as a function of overall physical health status. The findings emphasize the importance of measuring activity limitations distinctly from chronic conditions and impairments, and, perhaps, of measuring impairments distinctly from chronic conditions, and of comparing children with such health problems to children without health problems in order to obtain a more accurate picture of the impact of health on children's lives. The World Health Organization's distinct definitions of health condition and disability facilitate a dimensional approach for describing child health that can serve to clarify this field of study and improve comparability of data across countries. [ABSTRACT FROM AUTHOR]

This article presents a life needs model of pediatric service delivery that is based on the values of the intrinsic worth, dignity, and strengths of individuals. This developmental, socio-ecological model outlines the major types of service delivery needs of children and youth with disabilities, their families, and their communities within three spheres of life (the personal, interpersonal, and external spheres). The model legitimizes the concept of need, emphasizes the values of family-centered services, and recognizes child and family strengths and capacities. We discuss the utility of this transdisciplinary model in guiding pediatric service delivery to meet the long-range goals of community participation and quality of life of children and youth with disabilities. [ABSTRACT FROM AUTHOR]

Maternal (F 0 ) exposure to late-gestation heat stress reduces their daughter's (F 1 ) mammary gland fat pad (FP) mass, parenchyma (PAR) mass, and epithelial cell proliferation when evaluated at birth and weaning, and the daughters go on to produce less milk in their first lactation. Herein, we investigated the effect of maternal late-gestation heat stress on whole-body growth and mammary development of their granddaughters (F 2 ). Multiparous F 0 cows had access to heat abatement (n = 41, shade, and active cooling via fans and water soakers) or not (n = 41, shade only) for the last 56 d of gestation during a subtropical summer. Consequently, the F 1 daughters, born to F 0 cows, were heat-stressed (HT F1 , n = 36) or cooled (CL F1 , n = 37) in utero during the last 2 mo of gestation. All F 1 heifers were raised as an identically managed cohort until first calving. The F 2 granddaughters, born to HT F1 (HT F2 , n = 12) or CL F1 (CL F2 , n = 17), were raised as an identically managed cohort until 70 d of age. Dry matter intake, BW, hip height, wither height, chest girth, head circumference, mammary gland teat length, and left-right and front-rear teat distances were measured. Average daily gain was calculated for the preweaning period (0-49 d). Mammary ultrasounds were performed on d 21, 49, and 70 (n = 9/group) on the rear left and right quarters to quantify PAR and FP areas. Mammary biopsies were collected for histological evaluation of epithelial structures (hematoxylin and eosin staining), and to quantify cells positive for estrogen receptor, α subunit (ERα), cell proliferation (Ki67), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling, TUNEL). Heifer growth from birth to d 49 was similar between CL F2 and HT F2 for all parameters evaluated. Distances between teats and teat length were not different between groups. On d 70, CL F2 heifers tended to have a greater average PAR (right and left quarters) relative to HT F2 heifers. Although the left FP was smaller in HT F2 heifers relative to CL F2 heifers, the average FP was not different. The lumenal and nonlumenal epithelial structures in the PAR of HT F2 heifers were significantly smaller than those of CL F2 heifers. In addition, HT F2 heifers had a reduced percentage of proliferating cells in the epithelial and stromal compartments and a greater percentage of apoptotic cells, particularly in the stroma. The percentage of ERα positive cells was significantly reduced in HT F2 heifers. In summary, although HT F2 heifers' DMI was similar and they grew at the same rate as CL F2 heifers throughout the preweaning phase, their mammary glands had smaller PAR areas with fewer epithelial structures characterized by reduced cell turnover and lower ERα expression. These early changes in the microstructure and cellular turnover of the mammary gland may partly explain the reduction in lactation performance relative to CL F2 counterparts at maturity., (© 2024, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Maternal heat stress during late pregnancy can lead to intrauterine hyperthermia and affect fetal hypothalamic-pituitary-adrenal axis development and function. Herein, we investigated the effects of chronic environmental heat stress exposure of Holstein cows in the last 2 mo of gestation on their offspring's adrenal gland histomorphology and transcriptome. Cows in their last 54 ± 5 d of gestation were either heat stressed (housed under the shade of a freestall barn) or provided heat stress abatement via active cooling (via water soakers and fans) during a subtropical summer (temperature-humidity index >68). Respiration rate (RR) and skin temperature (ST) were elevated in heat-stressed dams relative to the cows with access to heat abatement (23 breaths/min and 2°C higher for RR and ST, respectively). Heifers born to heat-stressed cows experienced heat stress in utero (HS), whereas heifers born to actively cooled cows did not (CL). The adrenal gland was harvested from 6 heifers per group that were euthanized at birth (d 0; n = 12) or 1 wk after weaning (d 63; n = 12). Circulating cortisol was measured from blood samples collected weekly throughout the preweaning period. At d 63, heifers that experienced HS while developing in utero had heavier adrenal glands, with a greater total tissue surface area and thickness of the zona glomerulosa (ZG), fasciculata (ZF), and reticularis (ZR), compared with CL heifers. In addition, the adrenal gland of HS heifers had fewer cells in the ZG, more and larger cells in the ZF, and larger cells in the ZR, relative to CL heifers. Although no changes in circulating cortisol were observed through the preweaning period, the transcriptomic profile of the adrenal tissue was altered by fetal exposure to hyperthermia. Both at birth and on d 63, approximately 30 pathways were differentially expressed in the adrenal glands of HS heifers relative to CL. These pathways were associated with immune function, inflammation, prolactin signaling, cell function, and calcium transport. Upstream regulators significantly activated or inhibited in the adrenal glands of heifers exposed to intrauterine hyperthermia were identified. Maternal exposure to heat stress during late gestation caused an enlargement of their offspring's adrenal glands by inducing ZG and ZF cell hypertrophy, and caused gene expression changes. These phenotypic, histological, and molecular changes in the adrenal gland might lead to alterations in stress, immune, and metabolic responses later in life., (© 2024, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Dairy producers are experiencing production and animal welfare pressures from the increasing frequency and severity of heat stress events due to global climate change. Offspring performance during the preweaning and lactating periods is compromised when exposed to heat stress during late gestation (in utero). However, knowledge of the lingering effects of in utero heat stress on yearling dairy heifers is limited. Herein, we investigated the long-term effects of in utero heat stress on heifer growth, feed efficiency, and enteric methane emissions in postpubertal heifers. During the last 56 d of gestation, 38 pregnant cows carrying heifer calves were exposed to either heat stress (IUHT; n = 17) or artificial cooling (IUCL; n = 21). At 18 ± 1 mo of age, the resulting IUCL and IUHT heifers were enrolled in the present 63-d study. Heifers were blocked by weight and randomly assigned to 3 pens with Calan gates. Body weights were recorded on 3 consecutive days at the start and end of the trial and used to calculate ADG. Body condition score, hip width, body length, and chest girth were measured at the start and end of the study. All heifers were fed a TMR comprised of 46.6% oatlage, 44.6% grass/alfalfa haylage, 7.7% male-sterile corn silage, 0.3% urea, and 0.8% mineral/vitamin supplement (on a DM basis). The TMR and refusal samples were obtained daily, composited weekly, and dried to calculate DMI. During the study, each pen had access to a GreenFeed unit for 8 ± 1d to measure CH 4 and CO 2 gas fluxes. During the last 3 d of measuring CH 4 and CO 2 fluxes, fecal samples were collected, composited by animal, dried, and analyzed to calculate NDF, OM, and DM digestibility. On the last day of fecal sampling, blood samples were also collected via coccygeal venipuncture, and GC time-of-flight MS analysis was performed. Residual feed intake (RFI; predicted DMI - observed DMI), and feed conversion efficiency (FCE; DMI/ADG) were calculated to estimate feed efficiency. No differences were found in initial or final BW, hip width, chest girth, or BCS; however, IUCL heifers were longer in body length compared with IUHT heifers. Dry matter intake, ADG, RFI, and FCE were similar between IUHT and IUCL heifers. In utero heat-stressed and IUCL heifers produced similar amounts of CH 4 and CO 2 , and no differences were found in the number of GreenFeed visits or latency to approach the GreenFeed. The concentrations of 6 blood metabolites involved in lipogenic pathways were different between in utero treatments. In conclusion, in utero heat stress does not seem to have long-term effects on feed efficiency or methane emissions during the postpubertal growing phase; however, IUCL heifers maintained a body-length advantage over their IUHT counterparts and differed in concentrations of several candidate metabolites that encourage further exploration of their potential function in key organs, such as the liver and mammary gland., (© 2024, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Dairy cows experiencing heat stress (HS) during the pre-calving portion of the transition period give birth to smaller calves and produce less milk and milk protein. Supplementation of rumen-protected methionine (RPM) has been shown to modulate protein, energy, and placenta metabolism, making it a potential candidate to ameliorate HS effects. We investigated the effects of supplementing RPM to transition cows under HS induced by electric heat blanket (EHB) on cow-calf performance. Six weeks before expected calving, 53 Holstein cows were housed in a tie-stall barn and fed a control diet (CON, 2.2% Met of MP) or a CON diet supplemented with Smartamine®M (MET, 2.6% Met of MP, Adisseo Inc., France). Four weeks pre-calving, all MET and half CON cows were fitted with an EHB. The other half of the CON cows were considered thermoneutral (TN), resulting in 3 treatments: CONTN (n = 19), CONHS (n = 17), and METHS (n = 17). Respiratory rate (RR), skin temperature (ST), and rectal temperature (RT) were measured thrice weekly and core body temperatures recorded bi-weekly. Post-calving body weights (BW) and BCS were recorded weekly, and DMI was calculated and averaged weekly. Milk yield was recorded daily and milk components were analyzed every third DIM. Biweekly AA and weekly nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHB), insulin, and glucose were measured from plasma. Calf birth weight and 24 h growth, thermoregulation, and hematology profile were measured and apparent efficiency of absorption (AEA) of immunoglobulins was calculated. Data were analyzed using the MIXED procedure of SAS with 2 preplanned orthogonal contrasts: CONTN vs. the average of CONHS and METHS (C1) and CONHS vs. METHS (C2). Relative to TN, EHB cows had increased RT during the post-calving weeks and increased RR and ST during the entire transition period. Body weight, BCS, DMI, and milk yield were not impacted by the EHB or RPM. However, protein % and SNF were lower in CONHS, relative to METHS cows. At calving, METHS dams had higher glucose concentrations, relative to CONHS, and during the post-calving weeks, the EHB cows had lower NEFA concentrations than TN cows. Calf birthweight and AEA were reduced by HS, while RR was increased by HS. Calf withers height tended to be shorter and RT were lower in CONHS, compared with MTHS heifers. Overall, RPM supplementation to transition cows reverts the negative impact of HS on blood glucose concentration at calving and milk protein % in the dams and increases wither height while decreasing RT in the calf., (© 2024, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

During lactation, the murine mammary gland is responsible for a significant increase in circulating serotonin. However, the role of mammary-derived serotonin in energy homeostasis during lactation is unclear. To investigate this, we utilized C57/BL6J mice with a lactation and mammary-specific deletion of the gene coding for the rate-limiting enzyme in serotonin synthesis (TPH1, Wap-Cre x TPH1FL/FL) to understand the metabolic contributions of mammary-derived serotonin during lactation. Circulating serotonin was reduced by approximately 50% throughout lactation in Wap-Cre x TPH1FL/FL mice compared to wild-type mice (TPH1FL/FL), with mammary gland and liver serotonin content reduced on L21. The Wap-Cre x TPH1FL/FL mice had less serotonin and insulin immunostaining in the pancreatic islets on L21, resulting in reduced circulating insulin but no changes in glucose. The mammary glands of Wap-Cre x TPH1FL/FL mice had larger mammary alveolar areas, with fewer and smaller intra-lobular adipocytes, and increased expression of milk protein genes (e.g., WAP, CSN2, LALBA) compared to TPH1FL/FL mice. No changes in feed intake, body composition, or estimated milk yield were observed between groups. Taken together, mammary-derived serotonin appears to contribute to the pancreas-mammary cross-talk during lactation with potential implications in the regulation of insulin homeostasis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Field et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In dairy cows, the lactating mammary glands synthesize serotonin, which acts in an autocrine-paracrine manner in the glands and is secreted into the periphery. Serotonin signaling during lactation modulates nutrient metabolism in peripheral tissues such as adipose and liver. We hypothesized that the elevation of circulating serotonin during lactation would increase nutrient partitioning to the mammary glands, thereby promoting milk production. Our objective was to elevate circulating serotonin via intravenous infusion of the serotonin precursor 5-hydroxytryptophan (5-HTP) to determine its effects on mammary supply and extraction efficiency of AA, and milk components production. Twenty-two multiparous mid-lactation Holstein cows were intravenously infused with 5-HTP (1 mg/kg body weight) or saline, in a crossover design with two 21-d periods. Treatments were infused via jugular catheters for 1 h/d, on d 1 to 3, 8 to 10, and 15 to 17 of each period, to maintain consistent elevation of peripheral serotonin throughout the period. Milk and blood samples were collected in the last 96 h of each period. Whole-blood serotonin concentration was elevated above saline control for 96 h after the last 5-HTP infusion. Dry matter intake was decreased for cows receiving 5-HTP, and on average they lost body weight over the 21-d period, in contrast to saline cows who gained body weight. Milk production and milk protein yield were lower in cows receiving 5-HTP during the 3 infusion days, but both recovered to saline cow yields in the days after. Although milk fat yield exhibited a day-by-treatment interaction, no significant difference occurred on any given day. Milk urea nitrogen concentration was lower in 5-HTP cows on the days following the end of infusions, but not different from saline cows on infusion days. Meanwhile, plasma urea nitrogen was not affected by 5-HTP infusion. Circulating concentrations of AA were overall transiently decreased by 5-HTP, with concentrations mostly returning to baseline within 7 h after the end of 5-HTP infusion. Mammary extraction efficiency of AA was unaffected by 5-HTP infusion. Overall, both lactation performance and circulating AA were transiently reduced in cows infused with 5-HTP, despite sustained elevation of circulating serotonin concentration., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Cold and heat stress present welfare challenges for dairy calves. The consequences of thermal stress on biological functioning have been well documented, and many housing and management strategies have been evaluated to mitigate those detrimental impacts. In cold weather, mitigation strategies have largely focused on nutritional interventions or limiting heat loss with resources such as bedding or jackets. In hot weather, heat abatement strategies such as supplemental shade, increased environmental air exchange through passive ventilation, and forced air movement through mechanical ventilation have been evaluated. Recently in Wisconsin's continental climate, our group evaluated how 2 aspects of calf welfare-the needs for thermal comfort and social contact (i.e., pair or group housing vs. individual housing)-may align or conflict in winter and summer, respectively. In both seasons, calves pair-housed in outdoor hutches preferred social proximity. When 2 calves shared a hutch, the heat load was greater than for a single calf, which may be beneficial for thermal comfort in winter. In summer, the potential detriments from the additional heat load of 2 calves was mitigated with passive hutch ventilation, which calves preferred. Nonetheless, knowledge gaps remain regarding the impacts of thermal stress on calves' affective states, and much remains unknown about their preferences and motivations for specific thermal stress mitigation resources. Future research to address these gaps could improve our understanding of calf welfare and inform best practices for calf management., (© 2023.)

Although active ventilation via fans is an effective and widely adopted heat abatement method for use with adult dairy cattle, it has yet to be investigated in outdoor hutch-housed dairy calves despite most US calves being raised in such systems. We investigated a solar-powered fan system for outdoor calf hutches and its effect on hutch microclimate and calf thermoregulation. During summer, a 3 × 3 Latin square was replicated 4 times (n = 12 preweaning heifers) with 4-d exposure periods to minimally (CON; rear windows closed), passively (PASS; rear windows opened), or actively (ACT; solar-powered fan, activated at dry bulb temperature [T db ] > 21°C) ventilated hutch systems. Hutch microclimate and calf thermoregulation were evaluated either continuously (T db , humidity, rectum surface temperature, and behavior) or after a daily 30-min inside restriction (air speed, air particle number, noise level, respiration, and sweating rate, and skin and rectal temperature). Active ventilation substantially increased hutch air speed relative to PASS and CON (1.76 vs. 0.19 vs. 0.05 m/s). However, PASS hutches had the lowest INT T db (27.2 vs. 26.4 vs. 27.8°C), whereas ACT INT T db was reduced at 0900 and 1000 h relative to CON but not PASS. Similarly, ACT reduced calf respiration rates and lowered rectum surface temperature at 0800 and 0900 h when compared with CON but not PASS. The lack of strong ACT influence on calf outcomes over PASS could partially be explained by the decreased proportion of time ACT calves spent inside their hutch (48.7 vs. 67.3 vs. 64.1% of each hour). Overall, ACT improved hutch microclimate and calf responses relative to CON but not PASS. Either ACT or PASS ventilation may be sufficient to provide heat abatement to continental hutch-housed calves., (© 2023.)

Epidemiological data demonstrate that bovine whole milk is often substituted for human milk during the first 12 months of life and may be associated with adverse infant outcomes. The objective of this study is to interrogate the human and bovine milk metabolome at 2 weeks of life to identify unique metabolites that may impact infant health outcomes. Human milk ( n = 10) was collected at 2 weeks postpartum from normal-weight mothers (pre-pregnant BMI < 25 kg/m 2 ) that vaginally delivered term infants and were exclusively breastfeeding their infant for at least 2 months. Similarly, bovine milk ( n = 10) was collected 2 weeks postpartum from normal-weight primiparous Holstein dairy cows. Untargeted data were acquired on all milk samples using high-resolution liquid chromatography-high-resolution tandem mass spectrometry (HR LC-MS/MS). MS data pre-processing from feature calling to metabolite annotation was performed using MS-DIAL and MS-FLO. Our results revealed that more than 80% of the milk metabolome is shared between human and bovine milk samples during early lactation. Unbiased analysis of identified metabolites revealed that nearly 80% of milk metabolites may contribute to microbial metabolism and microbe-host interactions. Collectively, these results highlight untargeted metabolomics as a potential strategy to identify unique and shared metabolites in bovine and human milk that may relate to and impact infant health outcomes.

Homeostasis and thermoregulation are influenced by the interplay of hair coat and skin characteristics. Our previous work indicated that hair and skin adaptations, triggered by in utero heat stress, affect thermoregulation in postnatal life. Herein, we investigate multigenerational carry-over effects of late-gestation heat stress on hair and skin characteristics beyond the first generation. Pregnant Holstein dams (F 0 , grand-dams) were heat stressed (HT, shade, n = 41) or provided active cooling (CL, shade, fans, and water soakers, n = 41) for the last 56 d of gestation during summer (temperature-humidity index ≥68). The first generation of heifers (F 1, daughters) who were in utero heat stressed (HT F1 , n = 36) or not (CL F1 , n = 37) were born and raised as a cohort from birth to first calving. Thirty second-generation heifers (F 2 , granddaughters), born to HT F1 (HT F2 , n = 12) and CL F1 (CL F2 , n = 18), were raised as a cohort from birth to 70 d of age. Hair samples and skin biopsies from HT F2 and CL F2 were collected on postnatal d 70 (n = 6/group). Hair samples were subdivided into topcoat and undercoat, and skin tissue was fixed for ~18 h in 10% formalin, dehydrated, paraffin-embedded, sectioned, and stained with hematoxylin and eosin to visualize morphology. Variables analyzed included hair length and diameter; stratum corneum cross-sectional area and thickness; epidermis thickness; sweat gland depth, number, cross-sectional area, and average size; and sebaceous gland number, cross-sectional area, and average size. Measurements were performed using the ImageJ software and analyzed using PROC MIXED in SAS (SAS Institute Inc.). Hair length and diameter tended to be shorter and thicker in HT F2 , compared with CL F2 . The HT F2 skin had smaller stratum corneum cross-sectional area and tended to a thinner epidermis. to CL F2 , HT F2 skin had more but smaller sebaceous glands, whereas no differences in sweat glands were observed. In summary, we report phenotypic alterations in hair and skin characteristics of granddaughters. Whether these adaptations grant improved postnatal thermoregulatory ability for the granddaughters remains to be investigated., (© 2023.)

Grazing livestock in subtropical and tropical regions are susceptible to prolonged exposition to periods of extreme environmental conditions (i.e., temperature and humidity) that can trigger heat stress (HS). Currently, there is limited information on the effects of HS in the cow-calf sector globally, including in the southern U.S., as well as on mitigation strategies that could be implemented to improve animal well-being and performance. This study evaluated the impact of artificial shade (SHADE vs. NO SHADE) and breed (ANGUS vs. BRANGUS) on performance of pregnant-lactating cows, nursing heifers, and their subsequent offspring. Twenty-four Angus and 24 Brangus black-hided cows [579 ± 8 kg body weight (BW); approximately 85 d of gestation] and their nursing heifers (approximately 174 d of age) were randomly allocated to 12 'Pensacola' bahiagrass pastures (Paspalum notatum Flüggé; 1.3 ha, n = 4 pairs/pasture), with or without access to artificial shade [NO SHADE BRANGUS (NSB), NO SHADE ANGUS (NSA), SHADE BRANGUS (SB), and SHADE ANGUS (SA)] for 56 d that anticipated weaning during the summer season in Florida. Body condition score (BCS) of cows, blood samples, and BW of cow-calf pairs were obtained every 14 d during the 56-d experimental period until weaning. Following weaning (d 56), treatments were ceased, and cows and weaned heifers were managed alike. Weaned heifers were randomly allocated to 4 pens (n = 12/pen) equipped with GrowSafe feed bunks for 14 d to assess stress responses during weaning via plasma haptoglobin. An effect of SHADE × BREED interaction was detected for cow ADG, BW change, final BW, and final BCS, where SB had the greatest ADG, BW change, final BW, and final BCS. On d 14, SA cows had the greatest concentrations of insulin whereas on d 28 NSB had the lowest concentrations, NSA the greatest, and SA and SB being intermediate. On d 56, SA tended to have the greatest plasma insulin concentrations and SB the lowest. Weight gain per area (kg/ha) tended to be 11.4 kg/ha greater in SHADE vs. NO SHADE pastures. Pre-weaning calf ADG tended to be 0.14 kg greater for SHADE vs. NO SHADE calves. Weaning weight and BW at 14-d post-weaning were lesser for NSB vs. NSA, SA, and SB, whereas no differences in postweaning ADG or haptoglobin were observed. Effects of SHADE × BREED × day interaction was detected on plasma concentrations of IGF-1, in which NSA heifers had the lowest concentrations on weaning day. Gestation length was greater for SHADE vs. NO SHADE cows, but with no impacts on subsequent calf birth and weaning weight. In summary, providing artificial shade to pregnant-lactating beef cows increased body weight gain of nursing heifers and Brangus cows, while no impact on Angus dams were observed. The provision of artificial shade during the first trimester of gestation did not alter growth performance of the subsequent offspring at birth and weaning even though gestation length was longer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 M. Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Paraneoplastic neurological syndromes (PNS) include any symptomatic and non-metastatic neurological manifestations associated with a neoplasm. PNS associated with antibodies against intracellular antigens, known as "high-risk" antibodies, show frequent association with underlying cancer. PNS associated with antibodies against neural surface antigens, known as "intermediate- or low-risk" antibodies, are less frequently associated with cancer. In this narrative review, we will focus on PNS of the central nervous system (CNS). Clinicians should have a high index of suspicion with acute/subacute encephalopathies to achieve a prompt diagnosis and treatment. PNS of the CNS exhibit a range of overlapping "high-risk" clinical syndromes, including but not limited to latent and overt rapidly progressive cerebellar syndrome, opsoclonus-myoclonus-ataxia syndrome, paraneoplastic (and limbic) encephalitis/encephalomyelitis, and stiff-person spectrum disorders. Some of these phenotypes may also arise from recent anti-cancer treatments, namely immune-checkpoint inhibitors and CAR T-cell therapies, as a consequence of boosting of the immune system against cancer cells. Here, we highlight the clinical features of PNS of the CNS, their associated tumors and antibodies, and the diagnostic and therapeutic strategies. The potential and the advance of this review consists on a broad description on how the field of PNS of the CNS is constantly expanding with newly discovered antibodies and syndromes. Standardized diagnostic criteria and disease biomarkers are fundamental to quickly recognize PNS to allow prompt treatment initiation, thus improving the long-term outcome of these conditions.

Energy partitioning in lactating cows affects milk production, feed efficiency, and body reserves, with the latter having health implications for the transition into the following lactation. One molecule likely involved in the regulation of energy partitioning is serotonin. The objective of this experiment was to explore how increasing circulating serotonin, by intravenous infusion of the serotonin precursor 5-hydroxytryptophan (5-HTP), affects metabolic responses to a glucose challenge in midlactation cows as a means to manipulate energy partitioning. We intravenously infused Holstein cows with 5-HTP (1 mg/kg bodyweight dissolved in saline, n = 11) or saline alone as control (n = 9) over 1 h/day for 3 days. Cows were fasted overnight on day 2. On day 3, fasted cows were given an intravenous bolus of glucose (0.092 g/kg bodyweight). Blood samples were collected for the following 120 min for metabolic and hormonal analysis. Infusion of 5-HTP elevated circulating concentrations of serotonin and free fatty acids, reduced the concentration of insulin and amino acids, and did not affect the concentration of glucose and glucagon before the glucose challenge. Surrogate insulin sensitivity indices indicated improved insulin sensitivity in 5-HTP cows, but due to the unique metabolism of lactating ruminants, these index changes may instead reflect effects in insulin-independent glucose disposal, like milk synthesis. Challenging 5-HTP-treated cows with a glucose bolus reduced the insulin spike and blunted the decrease in free fatty acids, compared to saline cows, without changing glucose dynamics. Overall, these results suggest that serotonin stimulates insulin-independent glucose disposal, requiring less insulin to maintain normoglycemia.

Uterine diseases and heat stress (HS) are major challenges for the dairy cow. Heat stress alters host immune resilience, making cows more susceptible to the development of uterine disease. Although HS increases the incidence of uterine disease, the mechanisms by which this occurs are unclear. We hypothesize that evaporative cooling (CL) to alleviate HS in prepartum cows has carry-over effects on postpartum innate immunity. Nulliparous pregnant Holstein heifers were assigned to receive either forced CL that resulted in cool conditions (shade with water soakers and fans; n = 14) or to remain under HS conditions (barn shade only; n = 16) for 60 d prepartum. Postpartum, all cows were housed in a freestall barn equipped with shade, water soakers, and fans. Respiratory rate and rectal temperature during the prepartum period were greater in HS heifers compared with CL heifers, indicative of HS. Although milk production was decreased in HS cows compared with CL cows, the incidence of uterine disease and content of total or pathogenic bacteria in vaginal mucus on d 7 or d 21 postpartum was not affected by treatment. Whole blood was collected on d 21 and subjected to in vitro stimulation with lipopolysaccharide. Lipopolysaccharide-induced accumulation of IL-1β, IL-10, and MIP-1α was greater in blood collected from HS cows compared with CL cows. Our results imply that prepartum HS during late pregnancy has carry-over effects on postpartum innate immunity, which may contribute to the increased incidence of uterine disease observed in cows exposed to prepartum HS., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Prenatal hyperthermia has immediate and long-term consequences on dairy cattle growth, immunity, and productivity. While changes in the molecular architecture are reported in the mature mammary gland (MG), any influence on early-life mammary development is unknown. Herein, we characterize the impact of late-gestation in utero heat stress on heifer mammary gross and cellular morphology at early-life developmental stages (i.e., birth and weaning). During summer, pregnant dams were exposed to environmental heat stress (shade of a free-stall barn) or offered active cooling (shade, fans, and water soakers) for 54 ± 5 d before parturition (avg. temperature-humidity index = 79). Heifer calves born to these dams were either in utero heat-stressed (IU-HT; n = 36) or in utero cooled (IU-CL; n = 37) and were managed as a single cohort thereafter. A subset of heifers was euthanized at birth (d0; n = 8/treatment; 4.6 ± 2.3 h after birth) and after weaning (d63; n = 8/treatment; 63.0 ± 1.5 d) to harvest the whole MG. An ultrasound of rear mammary parenchyma (MPAR) was taken prior to d63 and correlated to harvested MPAR cross-sectional area and weight. Portions of mammary fat pad (MFP) and MPAR were preserved for compositional and histological analysis, including ductal structure number and cross-sectional area, connective tissue area, and adipocyte number and cross-sectional area. Cellular proliferation in MPAR was assessed via Ki-67 immunohistochemistry. Relative to IU-CL heifers, the MGs of IU-HT heifers were shorter in length at d0 and d63 (P ≤ 0.02). There were moderate correlations between d63 ultrasound and harvest measures. The IU-HT heifers had reduced MG and MFP mass at d0 and d63 (P ≤ 0.05), whereas MPAR mass was reduced only at d0 (P = 0.01). IU-HT heifers had greater MPAR protein and DNA content at d63 (P ≤ 0.04), but there were no MFP compositional differences (P ≥ 0.12). At d0, IU-HT heifers had fewer MPAR ductal structures (P ≤ 0.06), but there were no differences at d63. Yet, MPAR luminal and total ductal structure cross-sectional areas of IU-HT heifers were reduced at both d0 and d63 (P ≤ 0.01). The MFP adipocytes of IU-HT heifers were smaller at d0 (P ≤ 0.01), but differences were not detected at d63. The IU-HT heifers had diminished MPAR total, stromal, and epithelial cellular proliferation at both d0 and d63 (P < 0.01). Prenatal hyperthermia derails dairy calf early-life mammary development with potential carry-over consequences on future synthetic capacity., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The Centers for Disease Control and Prevention contracted with laboratories to sequence the SARS-CoV-2 genome from positive samples across the United States to enable public health officials to investigate the impact of variants on disease severity as well as the effectiveness of vaccines and treatment. Herein we present the initial results correlating RT-PCR quality control metrics with sample collection and sequencing methods from full SARS-CoV-2 viral genomic sequencing of 24,441 positive patient samples between April and June 2021., Methods: RT-PCR confirmed (N Gene Ct value < 30) positive patient samples, with nucleic acid extracted from saliva, nasopharyngeal and oropharyngeal swabs were selected for viral whole genome SARS-CoV-2 sequencing. Sequencing was performed using Illumina COVIDSeq™ protocol on either the NextSeq550 or NovaSeq6000 systems. Informatic variant calling, and lineage analysis were performed using DRAGEN COVID Lineage applications on Illumina's Basespace cloud analytical system. All sequence data and variant calls were uploaded to NCBI and GISAID., Results: An association was observed between higher sequencing coverage, quality, and samples with a lower Ct value, with < 27 being optimal, across both sequencing platforms and sample collection methods. Both nasopharyngeal swabs and saliva samples were found to be optimal samples of choice for SARS-CoV-2 surveillance sequencing studies, both in terms of strain identification and sequencing depth of coverage, with NovaSeq 6000 providing higher coverage than the NextSeq 550. The most frequent variants identified were the B.1.617.2 Delta (India) and P.1 Gamma (Brazil) variants in the samples sequenced between April 2021 and June 2021. At the time of submission, the most common variant > 99% of positives sequenced was Omicron., Conclusion: These initial analyses highlight the importance of sequencing platform, sample collection methods, and RT-PCR Ct values in guiding surveillance efforts. These surveillance studies evaluating genetic changes of SARS-CoV-2 have been identified as critical by the CDC that can affect many aspects of public health including transmission, disease severity, diagnostics, therapeutics, and vaccines., (© 2022. The Author(s).)

Exposure to heat stress during a cow's dry period disrupts mammary gland remodeling, impairing mammary function and milk production during the subsequent lactation. Yet, proteomic changes in the mammary gland underlying these effects are not yet known. We investigated alterations in the mammary proteome and phosphoproteome during lactation as a result of dry period heat stress using an isobaric tag for relative and absolute quantitation (iTRAQ)-based approach. Cows were cooled (CL; n = 12) with fans and water soakers in a free stall setting or were heat stressed through lack of access to cooling devices (HT; n = 12) during the entire dry period (approximately 46 days). All cows were cooled postpartum. Mammary biopsies were harvested from a subset of cows (n = 4 per treatment) at 14, 42, and 84 days in milk. Overall, 251 proteins and 224 phosphorylated proteins were differentially abundant in the lactating mammary gland of HT compared to CL cows. Top functions of differentially abundant proteins and phosphoproteins affected were related to immune function and inflammation, amino acid metabolism, reactive oxygen species production and metabolism, tissue remodeling, and cell stress response. Patterns of protein expression and phosphorylation are indicative of increased oxidative stress, mammary gland restructuring, and immune dysregulation due to prior exposure to dry period heat stress. This study provides insights into the molecular underpinnings of disrupted mammary function and health during lactation arising from prior exposure to dry period heat stress, which might have led to lower milk yields., (© 2022. The Author(s).)

Serotonin (5-HT) is an autocrine-paracrine molecule within the mammary gland regulating homeostasis during lactation and triggering involution after milk stasis. Exposure of dairy cows to hyperthermia during the dry period alters mammary gland involution processes leading to reduced subsequent yields. Herein, primary bovine mammary epithelial cells (pBMEC) under thermoneutral (TN, 37 °C) or heat shock (HS, 41.5 °C) conditions were cultured with either 0, 50, 200, or 500 μM 5-Hydroxy-L-tryptophan (5-HTP; 5-HT precursor) for 8-, 12- or 24-h. Expression of 95 genes involved in 5-HT signaling, involution and tight junction regulation were evaluated using a Multiplex RT-qPCR BioMark Dynamic Array Circuit. Different sets of genes were impacted by 5-HTP or temperature, or by their interaction. All 5-HT signaling genes were downregulated after 8-h of HS and then upregulated after 12-h, relative to TN. After 24-h, apoptosis related gene, FASLG, was upregulated by all doses except TN-200 μM 5-HTP, and cell survival gene, FOXO3, was upregulated by HS-50, 200 and 500 μM 5-HTP, suggesting 5-HTP involvement in cell turnover under HS. Supplementing 5-HTP at various concentrations in vitro to pBMEC modulates the expression of genes that might aid in promoting epithelial cell turn-over during involution in dairy cattle under hyperthermia., (© 2022. The Author(s).)

Heat stress has well-known influences on dairy calf physiology, but less is understood about calf behavioral responses to heat stress. Herein, we evaluated milk replacer intake, standing activity, and lying behaviors of calves exposed to prenatal or postnatal heat stress or both. Holstein calves were born to dams experiencing heat stress (HT; shade of a freestall barn) or cooling (CL; shade, fans, and soakers) during late gestation [~44 d before calving, prenatal; mean daily temperature-humidity index (THI) = 78]. They were then subsequently exposed to postnatal heat stress (shade and natural ventilation of an open-sided barn) or cooling (shade of the barn and forced ventilation by fans) from birth to weaning (56 d; mean daily THI = 77; n = 12 per prenatal × postnatal treatment). Heat stress was confirmed by elevated respiration rate and rectal temperature of the prenatal dam and the postnatal calf. Calves were group-housed with automatic milk feeders, from which milk replacer (MR) intake was assessed. Calf behavior was monitored using loggers and video. Postnatal-HT calves tended to consume less MR per hour in the late morning and drank less MR per visit relative to postnatal-CL calves. Postnatal-HT calves spent more time lying laterally and less time lying sternally in a tucked position during overnight hours. Prenatal-HT calves stood longer across the day, particularly overnight, compared with prenatal-CL calves. This study characterized behavioral responses of preweaning dairy calves exposed to chronic heat stress or active cooling during early-life developmental windows., (© 2021.)

Global rising temperature is a considerable threat to livestock production and an impediment to animal welfare. In fact, the 5 warmest years on record have occurred since 2016. Although the effect of heat stress on lactating cattle is well recognized and extensively studied, it is increasingly evident that rising temperatures will affect dairy cattle of all ages and lactation states. However, the extent and consequences of this effect are less understood and often overlooked in the literature and dairy industry. Early-life experiences, such as exposure to hyperthermia, can have life-long implications for health and productivity. This review highlights the body of work surrounding the effects of heat-stress exposure in young dairy cattle, including the prenatal fetus (in utero), postnatal calves (preweaning), and growing heifers, which are all categories that are typically not considered for heat-stress abatement on farm. Insights into the physiological and molecular mechanisms that might explain the adverse phenotypic outcomes of heat-stress exposure at different stages of development are also discussed. The estimated economic loss of in utero hyperthermia is addressed, and the ties between biological findings and opportunities for the application of cooling management interventions on farm are also presented. Our research highlights the importance of heat-stress abatement strategies for dry-pregnant cows to ensure optimal multigenerational productivity and showcases the benefits of cooling neonatal calves and growing heifers. Understanding the implications of heat stress at all life stages from a physiological, molecular, economic, and welfare perspective will lead to the development of novel and refined practices and interventions to help overcome the long-lasting effects of climate change in the dairy industry., (Copyright © 2021 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Dry period heat stress impairs subsequent milk production, but its impact on milk protein content and yield is inconsistent. We hypothesize that dairy cow exposure to dry period heat stress will reduce milk protein synthesis in the next lactation, potentially through modified amino acid (AA) transport and compromised mTOR signaling in the mammary gland. Cows were enrolled into heat-stressed (dry-HT, n = 12) or cooled (dry-CL, n = 12) treatments for a 46-day dry period then cooled after calving. Milk yield and composition and dry matter intake were recorded, and milk, blood, and mammary tissue samples were collected at 14, 42, and 84 days in milk (DIM) to determine free AA concentrations, milk protein fractions, and mammary AA transporter and mTOR pathway gene and protein expression. Dry matter intake did not significantly differ between treatments pre- or postpartum. Compared with dry-CL cows, milk yield was decreased (32.3 vs. 37.7 ± 1.6 kg/day) and milk protein yield and content were reduced in dry-HT cows by 0.18 kg/day and 0.1%. Further, dry-HT cows had higher plasma concentrations of glutamic acid, phenylalanine, and taurine. Gene expression of key AA transporters was upregulated at 14 and 42 DIM in dry-HT cows. Despite minor changes in mTOR pathway gene expression, the protein 4E-BP1 was upregulated in dry-HT cows at 42 DIM whereas Akt and p70 S6K1 were downregulated. These results indicate major mammary metabolic adaptations during lactation after prior exposure to dry period heat stress.

Maternal nutrition during gestation can cause epigenetic effects that translate to alterations in gene expression in offspring. This 2-year study employed RNA-sequencing technology to evaluate the pre- and post-vaccination muscle transcriptome of early-weaned Bos indicus-influenced beef calves born from dams offered different supplementation strategies from 57 ± 5 d prepartum until 17 ± 5 d postpartum. Seventy-two Brangus heifers (36 heifers/yr) were stratified by body weight and body condition score and assigned to bahiagrass pastures (3 heifers/pasture/yr). Treatments were randomly assigned to pastures and consisted of (i) no pre- or postpartum supplementation (NOSUP), (ii) pre- and postpartum supplementation of protein and energy using 7.2 kg of dry matter/heifer/wk of molasses + urea (MOL), or (iii) MOL fortified with 105 g/heifer/wk of methionine hydroxy analog (MOLMET). Calves were weaned on d 147 of the study. On d 154, 24 calves/yr (8 calves/treatment) were randomly selected and individually limit-fed a high-concentrate diet until d 201. Calves were vaccinated on d 160. Muscle biopsies were collected from the same calves (4 calves/treatment/day/yr) on d 154 (pre-vaccination) and 201 (post-vaccination) for gene expression analysis using RNA sequencing. Molasses maternal supplementation led to a downregulation of genes associated with muscle cell differentiation and development along with intracellular signaling pathways (e.g., Wnt and TGF-β signaling pathway) compared to no maternal supplementation. Maternal fortification with methionine altered functional gene-sets involved in amino acid transport and metabolism and the one-carbon cycle. In addition, muscle transcriptome was impacted by vaccination with a total of 2,396 differentially expressed genes (FDR ≤ 0.05) on d 201 vs. d 154. Genes involved in cell cycle progression, extracellular matrix, and collagen formation were upregulated after vaccination. This study demonstrated that maternal supplementation of energy and protein, with or without, methionine has long-term implications on the muscle transcriptome of offspring and potentially influence postnatal muscle development., Competing Interests: Authors received financial assistance for the completion of this project from University of Florida – Early Career Seed funding, Novus International (Romance, AR), and Zoetis Animal Health (Florham Park, NY). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Exposure to heat stress can alter the development and immune system function in dairy calves. Serotonin is an immunomodulatory biogenic amine that functions as a neurotransmitter and as a stress-response mediator. Our objectives were to characterize the patterns of serum serotonin concentrations and the pattern of serotonin-related genes expressed by immune cells of calves exposed to chronic heat stress or heat stress abatement during early life, and to explore whether these might relate to immune system development. Dairy calves were exposed to chronic heat stress (HS; n = 6) or heat stress abatement (cooling, CL; n = 6) across the prenatal (late gestation, last 46 d) and postnatal (from birth to weaning, 56 d) developmental windows. Blood samples were collected to harvest serum (weekly, from d 1 to 49), to isolate of circulating leukocyte mRNA (at 1, 21 and 42 d of age) and characterize immune cell populations by flow cytometry (at 21 and 47 d of age). Calves exposed to chronic heat stress pre- and postnatally had lower red blood cell counts and lower circulating serotonin, immunoglobulin G, and B-lymphocytes compared to CL calves. Circulating blood leukocyte mRNA expression of serotonin receptors -1A, -1F, -4 and -5 was greater, while heat shock protein 70 and immune-related genes (i.e., TBX21, TLR4, and TGFβ) were lower in HS relative to CL calves. Peripheral blood leukocytes from all calves secreted serotonin and interleukin-6 after in-vitro lipopolysaccharide stimulation. However, the HS calves produced more serotonin and less interleukin-6 than CL calves when activated in-vitro. Together, our data suggest that providing heat stress abatement to dairy calves across prenatal and postnatal developmental windows might modulate the serotonin synthesis pathway in ways that may benefit humoral immunity against microbial pathogens., Competing Interests: The authors acknowledge the support of Southeast Milk Check-off to JL for previous related work. Southeast Milk had no role in funding this study, or any role in any other aspect of this study.

Temperature affects many life processes, but its effect might be expected to differ among eukaryotic organisms inhabiting similar environments. We reviewed literature on temperature thresholds of humans, livestock, poultry, agricultural crops, and sparse examples of fisheries. We found that preferable and harmful temperatures are similar for humans, cattle, pigs, poultry, fish, and agricultural crops. Preferable temperatures range from 17°C to 24°C. Stress temperature thresholds are lower when humidity is higher. However, extended exposure to temperatures above 25°C with high humidity can cause heat stress in many organisms. Short exposures to temperatures above 35°C with high humidity, or above 40°C with low humidity, can be lethal. Increases in exposure, frequency, and duration of stressful and lethal temperatures increase the physiological stress and bodily damage suffered by humans, livestock, poultry, fish, and agricultural crops., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

In mammals, peripheral serotonin is involved in regulating energy balance. Herein, we characterized the transcriptomic profile and microstructure of adipose and muscle in pre-weaned calves with increased circulating serotonin. Holstein bull calves (21 ± 2 days old) were fed milk replacer supplemented with saline (CON, 8 mL/day n = 4) or 5-hydroxytryptophan (5-HTP, 90 mg/day, n = 4) for 10 consecutive days. Calves were euthanized on d10 to harvest adipose and muscle for RNA-Sequencing and histological analyses. Twenty-two genes were differentially expressed in adipose, and 33 in muscle. Notably, Interferon gamma inducible protein-47 was highly expressed and upregulated in muscle and adipose (avg. log FC = 6.5). Enriched pathways in adipose tissue revealed serotonin's participation in lipid metabolism and PPAR signaling. In muscle, enriched pathways were related to histone acetyltransferase binding, Jak-STAT signaling, PI3K-Akt signaling and cell proliferation. Supplementation of 5-HTP increased cell proliferation and total cell number in adipose and muscle. Adipocyte surface area was smaller and muscle fiber area was not different in the 5-HTP group. Manipulating the serotonin pathway, through oral supplementation of 5-HTP, influences signaling pathways and cellular processes in adipose and muscle related to endocrine and metabolic functions which might translate into improvements in calf growth and development.

An 81-year-old female presented with a right pontine infarct and later developed recurrent vivid hallucinations. After a workup for delirium and hallucinosis was unrevealing, a diagnosis of peduncular hallucinosis (PH) was proposed. Treatment with quetiapine and, later, adjunctive nightly melatonin resulted in return to cognitive baseline. An array of etiologies can be responsible for visual hallucinations, including PH. Herein, we review several disorders of hallucinosis and their diagnostic workup. Additionally, we explore the pathophysiology of PH and its association with the pontine-geniculate-occipital (PGO) pathway and propose why correction of the sleep-wake cycle may benefit patients with PH.

This experiment evaluated the effects of providing artificial shade during summer on activity, behavior, and growth performance of pregnant grazing beef heifers. Thirty-six black-hided Angus and Angus crossbred pregnant heifers [418 ± 9 kg body weight (BW); approximately 90 d of gestation] were stratified by breed, blocked by BW, and allocated to 12 "Pensacola" bahiagrass pastures ( Paspalum notatum Flüggé; 1.3 ha, n = 3 heifers/pasture) with or without access to artificial shade (SHADE vs. NO SHADE; 6 pastures each) for 7 wk during summer. The shade structures were composed of shade cloth (11 × 7.3 m length, 2.4 m height: 26.8 m 2 of shade per heifer). Shrunk BW was recorded on enrollment (day 0) and week 7 (day 47), whereas full BW was obtained on week 2 (day 14), 4 (day 28), and 6 (day 42) to assess average daily gain (ADG). Vaginal temperature was recorded for five consecutive days during weeks 1, 3, 5, and 7 using an intravaginal digital thermo-logger, and individual GPS devices were used to quantify the use of shade for an 8-h period. Activity was monitored using automated monitoring devices (HR-LDn tags SCR Engineers Ltd., Netanya, Israel) through the experimental period. Vaginal temperature was lower ( P < 0.01) for heifers in the SHADE compared with heifers in the NO SHADE treatment from 1200 to 1600 h and 1100 to 1900 h for weeks 1 and 3, respectively. Heifers in the SHADE treatment spent 70% of the 8-h period evaluated under the shaded structure. Provision of shade increased ( P < 0.01) daily lying time (11.4 ± 0.2 vs. 10.3 ± 0.2 h/d) and standing bouts per day ( P < 0.01; 12.6 ± 0.4 vs. 10.8 ± 0.4 bouts/d), whereas it reduced ( P < 0.01) standing bout duration (61.6 ± 3.0 vs. 82.9 ± 3.0 min/bout) relative to heifers without access to shade. The interaction between treatment and hour affected ( P < 0.01) daily rumination time because heifers with access to SHADE had greater rumination between 1000 and 1200 h. Although ADG tended ( P = 0.08) to be greater for the heifers in the SHADE treatment (0.20 vs. -0.02 kg, respectively), the access to shade did not ( P = 0.79) affect the final BW. In conclusion, providing artificial shade during summer to pregnant grazing beef heifers was effective in reducing vaginal temperatures and exerted changes in heifer behaviors that translated into slight improvements in growth performance., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Hormonal alterations occurring under late gestation heat stress may disturb mammary gland remodelling, resulting in a reduced milk yield during the subsequent lactation. We investigated the effects of an altered endocrine environment on mammary gene expression at different stages of the dry period. Mammary gland biopsies from in vivo-cooled (CL) or heat-stressed (HT) cows were collected at d 3 and 35 relative to dry-off and divided into explants. Explants were incubated in vitro for 24 h in one of three media: Basal: no prolactin or estrogen; CL-mimic: Basal + low prolactin + high 17β-estradiol, or HT-mimic: Basal + high prolactin + low 17β-estradiol. Real time qPCR was used to quantify gene expression. We established that late-gestation heat stress changes the expression of prolactin and oestrogen receptors, downregulates genes involved in apoptosis, autophagy and proliferation at d 3 and upregulates genes related to those cellular processes at d 35. Moreover, compared with in vivo treatments, we showed that the expression of fewer genes was impacted by in vitro treatments which aimed to mimic the hormonal response of cows exposed to a different environment. Further research will continue to uncover the mechanisms behind the production impairments caused by late-gestation heat stress.

High-throughput cell-data technologies such as single-cell RNA-seq create a demand for algorithms for automatic cell classification and characterization. There exist several cell classification ontologies with complementary information. However, one needs to merge them to synergistically combine their information. The main difficulty in merging is to match the ontologies since they use different naming conventions. Therefore, we developed an algorithm that merges ontologies by integrating the name matching between class label names with the structure mapping between the ontology elements based on graph convolution. Since the structure mapping is a time consuming process, we designed two methods to perform the graph convolution: vectorial structure matching and constraint-based structure matching. To perform the vectorial structure matching, we designed a general method to calculate the similarities between vectors of different lengths for different metrics. Additionally, we adapted the slower Blondel method to work for structure matching. We implemented our algorithms into FOntCell, a software module in Python for efficient automatic parallel-computed merging/fusion of ontologies in the same or similar knowledge domains. FOntCell can unify dispersed knowledge from one domain into a unique ontology in OWL format and iteratively reuse it to continuously adapt ontologies with new data endlessly produced by data-driven classification methods, such as of the Human Cell Atlas. To navigate easily across the merged ontologies, it generates HTML files with tabulated and graphic summaries, and interactive circular Directed Acyclic Graphs. We used FOntCell to merge the CELDA, LifeMap and LungMAP Human Anatomy cell ontologies into a comprehensive cell ontology. We compared FOntCell with tools used for the alignment of mouse and human anatomy ontologies task proposed by the Ontology Alignment Evaluation Initiative (OAEI) and found that the F β alignment accuracies of FOntCell are above the geometric mean of the other tools; more importantly, it outperforms significantly the best OAEI tools in cell ontology alignment in terms of F β alignment accuracies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past collaboration with one of the authors MA-B., (Copyright © 2021 Cabau-Laporta, Ascensión, Arrospide-Elgarresta, Gerovska and Araúzo-Bravo.)

Dry period heat stress impairs subsequent milk yield. Our objective was to evaluate the effect of heat stress or cooling during the early and late dry period on mammary gland gene expression and microstructure. Cows were dried off ∼45 d before expected parturition and randomly assigned to 1 of 2 treatments: heat stress (HT, n = 39) or cooling (CL, n = 39) during the first 21 d of the dry period. On d 22, cows were switched or remained on HT and CL and this yielded 4 treatments: heat stress during the entire dry period (HTHT, n = 18); cooling during the entire dry period (CLCL, n = 20); HT for the first 21 d dry, then CL until calving (HTCL, n = 21); or CL for the first 21 d dry, then HT until calving (CLHT, n = 19). Data were analyzed in 2 periods: first 21 d dry (early dry period) and from 22 d until calving (late dry period) and analyzed using PROC MIXED or GLM in SAS (SAS Institute Inc., Cary, NC). Mammary biopsies (5-8 cows/treatment) were collected at -3, 3, 7, 14, and 25 d relative to dry-off to evaluate mammary gland gene expression and histology [i.e., cellular apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling) and proliferation (Ki67)]. Mammary alveoli number and connective tissue were visualized by hematoxylin and eosin and Mason's trichrome staining, respectively. During the early dry period, CL upregulated expression of CASP3, IGF1R, HSP90, HSF1, BECN1, ATG3, ATG5, and PRLR-LF relative to HT. However, in the late dry period, CLHT treatment upregulated expression of CASP3, CASP8, HSP70, HSP90, PRLR-LF, STAT5, CSN2, and ATG3 relative to CLCL. During the early dry period, cows exposed to HT had reduced mammary and stroma cell apoptosis and proliferation relative to CL. In addition to these findings, cows exposed to HT had lower connective tissue 3 d after dry-off relative to CL. However, in the late dry period, HTHT cows had higher connective tissue relative to CLCL. Also, in the early dry period, cows exposed to HT had greater alveoli number relative to CL, and HT decreased expression of genes related to autophagy and apoptosis in the early dry period, consistent with a delay in involution with HT. Thus, cows exposed to HT have extended involution with delayed apoptosis and autophagy signaling. Also, HT compromises mammary gland cell proliferation and leads to higher connective tissue later in the dry period. These results provide evidence that heat stress impairs overall mammary gland turnover during the dry period, which then affects secretory activity and productivity in the next lactation., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Heat stress has a myriad of effects on dairy cattle across the life cycle. Whereas, the most commonly recognized impacts are associated with production responses, emerging evidence indicates that heat stress profoundly alters the immune response of calves and cows, from the prenatal stage through lactation. For example, in utero heat stress reduces passive immune transfer regardless of colostrum source, relative to normothermic conditions in late gestation. Dry cows exposed to heat stress have lower immunoglobulin responses to ovalbumin vaccination, but this effect dissipates with cooling following parturition. Conversely, cows under heat stress when dry exhibit carryover effects on the innate arm of the immune system in early lactation. In this paper we review the effects of heat stress throughout the life cycle of the dairy cow, with particular emphasis on the impact of heat stress during late gestation on the cow and the developing fetus, both before and after parturition. In addition, the impact of altered immune status under heat stress on other physiological systems, especially those supporting milk production, are considered. Finally, management interventions to prevent and reverse the effect of heat stress are presented., (Copyright © 2020 Dahl, Tao and Laporta.)

The objectives of the 2 studies conducted were to validate the accuracy of an automated monitoring device (AMD; HR-LDn tags, SCR Engineers Ltd., Netanya, Israel) for different types of behaviors or cow-states (side lying, resting, medium activity, high activity, rumination, grazing, walking, and panting) in beef heifers and to determine if the total time per cow-state recorded by the AMD corresponds to the total time per cow-state recorded by instantaneous observations. Cow-state is recorded every second and, within 1 min, the most prevalent cow-state is considered to be the behavior presented by the animal during that interval. Study personnel (n = 2) observed heifers (n = 10) for 20 min from 0800 to 1140 h and 10 min from 1500 to 1640 h during 4 consecutive days and recorded continuously each cow-state at started and ended. Thus, study personnel were able to determine within a 1-min interval, which cow-state was most prevalent and represented the heifer's behavior. Because the proprietary machine learning algorithm prioritizes certain behaviors over others based on their contribution to the understanding of generalized bovine behavior patterns, we also determined the most prevalent behavior observed in 5-min intervals. Test characteristics (sensitivity, specificity, accuracy, and negative and positive predicted values) were calculated using the observer as the gold standard. In study 2, heifer behavior was scanned by observers (n = 2) every 5 min from 0800 to 1100 h and 1500 to 1800 h for 3 consecutive days. Total minutes per cow-state according to the observer were compared with the total minutes per cow-state according to the AMD during the same period to determine the correlation coefficient. In study 1, test characteristics were high (low ≤ 40%, moderate = 41 to 74%, high ≥ 75%) for rumination (≥ 89.7%), grazing (≥ 76.5%), and side lying (≥ 81.8%), and moderate for resting (≥ 48.8%). In study 2, the correlation coefficient for rumination (R2 = 0.92) and grazing (R2 = 0.90) were high and the correlation coefficient for resting (R2 = 0.66) and walking (R2 = 0.33) were moderate. We conclude that the AMD used in this study showed high accuracy when measuring rumination and grazing, but it was subpar when measuring resting and walking. The algorithms employed by the AMD used need to be improved for determination of walking and resting behaviors of beef cattle., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The bovine dry period is a non-lactating period between consecutive lactations characterized by mammary gland involution and redevelopment phases to replace senescent mammary epithelial cells with active cells primed for the next lactation. Dairy cows exposed to heat stress during the dry period experience milk yield reductions between 3-7.5 kg/d in the next lactation, partially attributed to processes associated with mammary cell growth and turnover during the dry period. However, the carry-over impact of dry period heat stress on mammary morphology during lactation has yet to be determined. In the current study, we hypothesized that exposure to heat stress during the dry period would alter alveolar microstructure and cellular turnover (i.e. proliferation and apoptosis) during lactation. Cows were either subjected to heat stress (HT, access to shade; n = 12) or cooling (CL, access to shade, fans, and soakers; n = 12) for a 46 d dry period. Upon calving, all cows were treated similarly with access to cooling for their entire lactation. Six cows per treatment were randomly selected for mammary gland biopsies at 14, 42, and 84 days in milk. Tissues were sectioned and stained for histological analysis. During lactation, HT cows produced 4 kg less colostrum and 3.7 kg less milk compared with CL cows. Lactating mammary gland microstructure was impacted after exposure to dry period heat stress; HT cows had fewer alveoli and a higher proportion of connective tissue in the mammary gland relative to CL cows, however alveolar area was similar between treatments. Rates of mammary epithelial cell proliferation and apoptosis were similar between treatment groups. This suggests that heat stress exposure during the dry period leads to reductions in milk yield that could be caused, in part, by a reduction in alveoli number in the lactating mammary gland but not to dynamic alterations in cellular turnover once lactation is established., Competing Interests: The authors have declared that no competing interests exist.

Heat stress during late gestation adversely impacts the developing calf. Calves that experience heat stress are born at a lower bodyweight and those deficits persist at least until puberty. In utero heat stress reduces passive transfer and calf survival. Late gestation heat stress programs a phenotype with lower milk yield, relative to herd mates born to cooled dams, in the first lactation and subsequent lactations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cooling during the entire dry period abates the negative effects of heat stress postpartum, yet the temporal relationship of cooling (i.e., early or late dry period) to performance is unknown. We evaluated the effect of heat stress early, late, and for the entire dry period on subsequent performance. Cows were selected based on mature-equivalent milk yield and dried off 45 d before expected calving. Cows were blocked by parity, previous 305-d mature equivalent milk yield, and body weight (BW) and randomly assigned to cooling (shade, fans, and soakers; CL) or heat stress (shade; HT). Treatments included CL (n = 20) or HT (n = 18) during the entire dry period, HT during the first 3 wk dry and then CL until calving (HTCL, n = 21), or CL during the first 3 wk dry period and then HT until calving (CLHT, n = 19). Heat stress increased rectal temperature (RT; CL, 38.8; HT, 39.1 ± 0.04°C) and respiration rate (RR; CL, 52.9; HT, 70.5 ± 1.9 breaths/min) during the early dry period. In the late dry period, HT increased RT and RR relative to CL cows (RT = CL, 38.7; HT, 39.1; CLHT, 39.1; HTCL, 38.9 ± 0.05°C; RR = CL, 47; HT, 64; CLHT, 66; HTCL, 53 ± 2.1 breaths/min). During the early dry period, HT decreased dry matter intake (CL, 11.8; HT, 10.5 ± 0.35 kg/d) but dry matter intake did not differ among treatments during late dry period (HT, 10.7; HTCL, 11.1; CL, 11.2; CLHT, 10.1 ± 0.55 kg/d). Cows exposed to prepartum cooling during the entire dry period had increased dry matter intake compared with cows exposed to heat stress during the late dry period (CL vs. CLHT, 11.2 ± 0.55 and 10.1 ± 0.55 kg/d, respectively). Heat stress at any time reduced gestation length compared with cows under prepartum cooling during the entire dry period (CL, 277 vs. HT, 274; CLHT, 273; and HTCL, 274 ± 1.17 d). Dry period length decreased by approximately 4 d if cows were exposed to HT at any time. During the early dry period, HT decreased BW, whereas CL increased BW relative to that at dry-off (CL, 6.9; HT, -9.4 ± 3.7 kg). In the late dry period, we detected no differences in BW gain among treatments, but cows exposed to prepartum cooling for the entire dry period tended to have increased BW gain compared with HT and HTCL. Prepartum cooling during the early or late dry period alone partially rescued milk yield only in the first 3 wk of lactation (CL, 32.9; HT, 26.6; CLHT, 29.7; HTCL, 30.7 ± 1.37 kg/d). Cooling for the entire dry period increased milk yield up to 30 wk into lactation compared with all other treatments. Thus, HT at any time during the dry period compromises performance of cows after calving., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Heat stress during late gestation in cattle negatively affects the performance of the dam and its calf. This brief exposure to an adverse environment before parturition affects the physiological responses, tissue development, metabolism, and immune function of the dam and her offspring, thereby limiting their productivity. During the dry period of a dairy cow, heat stress blunts mammary involution by attenuating mammary apoptosis and autophagic activity and reduces subsequent mammary cell proliferation, leading to impaired milk production in the next lactation. Dairy cows in early lactation that experience prepartum heat stress display reduced adipose tissue mobilization and lower degree of insulin resistance in peripheral tissues. Similar to mammary gland development, placental function is impaired by heat stress as evidenced by reduced secretion of placental hormones (e.g., estrone sulfate) in late gestation cows, which partly explains the reduced fetal growth rate and lighter birth weight of the calves. Compared with dairy calves born to dams that are exposed to evaporative cooling during summer, calves born to noncooled dry cows maintain lower BW until 1 yr of age, but display a stronger ability to absorb glucose during metabolic challenges postnatally. Immunity of the calves, both passive and cell-mediated immune function, is also impaired by prenatal heat stress, resulting in increased susceptibility of the calves to diseases in their postnatal life. In fact, dairy heifers born to heat-stressed dry cows without evaporative cooling have a greater chance leaving the herd before puberty compared with heifers born to dry cows provided with evaporative cooling (12.2% vs. 22.7%). Dairy heifers born to late-gestation heat-stressed dry cows have lower milk yield at maturity during their first and second lactations. Emerging evidence suggests that late-gestation heat stress alters the mammary gland microstructure of the heifers during the first lactation and exerts epigenetic alterations that might explain, in part, their impaired productivity., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Earth's rising temperature has substantial repercussions for food-producing animals by increasing morbidity and mortality, diminishing reproductive potential, and reducing productivity. In the dairy industry this equates to massive losses in milk yield, which occur when cows are exposed to heat stress during lactation or during the non-lactating period between lactations (i.e. dry period). Furthermore, milk yield is significantly lower in first-lactation heifers that experienced fetal heat stress. The mechanisms underlying intrauterine effects of heat stress on the offspring's future lactation have yet to be fully elucidated. We hypothesize that heat stress experienced through the intrauterine environment will alter the mammary gland microstructure and cellular processes involved in cell turnover during the cow's first lactation. Mammary biopsies were collected from first-lactation heifers that were exposed to heat stress or cooling conditions while developing in utero (IUHT and IUCL; respectively, n = 9-10). IUHT heifers produced less milk compared to IUCL. The mammary glands of IUHT heifers differed morphologically from IUCL, with the IUHT heifers having smaller alveoli and a greater proportion of connective tissue relative to their IUCL herdmates. However, intrauterine heat stress had little impact on the proliferation and apoptosis of mammary cells during lactation. Our results indicate that fetal exposure to heat stress impairs milk production in the first lactation, in part, by inducing aberrant mammary morphology. This may result from alterations in the developmental trajectory of the fetal mammary gland that persist through the first lactation rather than to alterations in the cellular processes controlling mammary cell turnover during lactation., Competing Interests: The authors have declared that no competing interests exist.

The bovine dry period is a dynamic non-lactating phase where the mammary gland undergoes extensive cellular turnover. Utilizing RNA sequencing, we characterized novel genes and pathways involved in this process and determined the impact of dry period heat stress. Mammary tissue was collected before and during the dry period (-3, 3, 7, 14, and 25 days relative to dry-off [day 0]) from heat-stressed (HT, n = 6) or cooled (CL, n = 6) late-gestation Holstein cows. We identified 3,315 differentially expressed genes (DEGs) between late lactation and early involution, and 880 DEGs later in the involution process. DEGs, pathways, and upstream regulators during early involution support the downregulation of functions such as anabolism and milk component synthesis, and upregulation of cell death, cytoskeleton degradation, and immune response. The impact of environmental heat stress was less significant, yet genes, pathways, and upstream regulators involved in processes such as ductal branching morphogenesis, cell death, immune function, and protection against tissue stress were identified. Our research advances understanding of the mammary gland transcriptome during the dry period, and under heat stress insult. Individual genes, pathways, and upstream regulators highlighted in this study point towards potential targets for dry period manipulation and mitigation of the negative consequences of heat stress on mammary function.

Metritis is caused by polymicrobial infection; however, recent metagenomic work challenges the importance of known pathogens such as Escherichia coli and Trueperella pyogenes while identifying potential new pathogens such as Bacteroides pyogenes, Porphyromonas levii and Helcococcus ovis. This study aims to quantify known and emerging uterine pathogens, and to evaluate their association with metritis and fever in dairy cows. Metritis was diagnosed at 6 ± 2 days postpartum, a uterine swab was collected and rectal temperature was measured. 39 cows were classified into three groups: Healthy (n = 14), Metritis without fever (MNoFever; n = 12), and Metritis with fever (MFever; n = 13). Absolute copy number was determined for total bacteria and for 8 potentially pathogenic bacteria using droplet digital PCR. Both MNoFever and MFever cows had higher copy number of total bacteria, Fusobacterium necrophorum, Prevotella melaninogenica, Bacteroides pyogenes, Porphyromonas levii, and Helcococcus ovis than Healthy cows. MNoFever and MFever groups were similar. There was no difference among groups in copy number of Escherichia coli, Trueperella pyogenes, and Bacteroides heparinolyticus, and they all had low copy numbers. Our work confirms the importance of some bacteria identified by culture-based studies in the pathogenesis of metritis such as Fusobacterium necrophorum and Prevotella melaninogenica; however, it challenges the importance of others such as Escherichia coli and Trueperella pyogenes at the time of metritis diagnosis. Additionally, Bacteroides pyogenes, Porphyromonas levii, and Helcococcus ovis were recognized as emerging pathogens involved in the etiology of metritis. Furthermore, fever was not associated with the total bacterial load or specific bacteria., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Objectives: During the 2015-2016 academic year, Rocky Vista University College of Osteopathic Medicine (RVUCOM) conducted a required 1-week surgical simulation course as the first week of students' 8-week surgical clerkship. This course was adapted from a pilot RVUCOM surgical simulation course and other surgical simulation courses identified in the literature. The objectives of this course were to teach surgical skills and clinical knowledge, aid students in adjusting to the stress of a surgical clerkship, and improve students' confidence and abilities during the clerkship., Methods: In all, 148 students participated in the surgical simulation course. Subjective assessment of this course included each student completing a daily standardized stress survey and student feedback surveys at the end of the course and at the end of the surgical clerkship. Objective assessment of this course compared precourse and postcourse tests of surgical knowledge and instrument identification, as well as comparison of NBME Surgery Subject Assessment percentile ranks of this class with 3 prior classes., Results: Daily stress surveys indicated decreased stress on day 5 compared to day 1 (p < 0.01). Students' confidence level increased significantly on day 5 compared to day 1 (p < 0.01). Student feedback surveys demonstrated students' perception that surgical skills and clinical skills had been learned during the course and that the course improved their performance during the surgical clerkship. NBME Surgery Subject Assessment percentile rank improved significantly (p < 0.01) from a mean percentile rank of 36.94 for 3 previous classes to a mean percentile rank of 43.82 for the class who completed the simulation course. Surgical knowledge improved significantly (p < 0.001) from a pretest mean score of 47.02% to a posttest mean score of 55.14%. Surgical instrument identification improved significantly (p < 0.001) from a pretest mean of 13.81% to a posttest mean of 95.28%., Conclusion: The RVUCOM surgery simulation course significantly improved student performance academically and helped students acclimate to stress, increase their confidence level, and acquire surgical skills needed during the third-year surgery clerkship., (Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Heat stress during late gestation negatively affects the physiology, health, and productivity of dairy cows as well as the calves developing in utero. Providing cows with active cooling devices, such as fans and soakers, and supplementing cows with an immunomodulating feed additive, OmniGen-AF (OG; Phibro Animal Health Corporation), improves immune function and milk yield of cows. It is unknown if maternal supplementation of OG combined with active cooling during late gestation might benefit the developing calf as well. Herein we evaluated markers of innate immune function, including immune cell counts, acute phase proteins, and neutrophil function, of calves born to multiparous dams in a 2 × 2 factorial design. Dams were supplemented with OG or a bentonite control (NO) beginning at 60 d before dry off and exposed to heat stress with cooling (CL) or without active cooling (HT) during the dry period (∼46 d). At birth, calves were separated from their dams and fed 6.6 L of their dams' colostrum in 2 meals. Calf body weight and rectal temperature were recorded, and blood samples were collected at birth (before colostrum feeding) and at 10, 28, and 49 d of age. Calves born to either CL dams or OG dams were heavier at birth than calves born to HT or NO dams, respectively. Concentrations of serum amyloid A were higher in the blood of calves born to OG dams relative to NO and for HT calves relative to CL calves. In addition, calves born to cooled OG dams had greater concentrations of plasma haptoglobin than calves born to cooled control dams. Neutrophil function at 10 d of age was enhanced in calves born to cooled OG dams and lymphocyte counts were higher in calves born to OG dams. Together these results suggest that adding OG to maternal feed in combination with active cooling of cows during late gestation is effective in mitigating the negative effects of in utero heat stress on postnatal calf growth and immune competence., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Heat stress in dairy cows during the dry period impairs milk yield in the next lactation. Feeding OmniGen-AF (OG; Phibro Animal Health Corp., Teaneck, NJ) to lactating cows during heat stress may increase dry matter intake (DMI) and lowers respiration rate (RR) and rectal temperature (RT), but the effects in dry cows are not known. We hypothesized that OG supplementation before, during, and after the dry period (approximately 160 d total) would overcome the effects of heat stress and improve cow performance in the next lactation. Cows were randomly assigned to OG or control (placebo) treatments for the last 60 d in milk (DIM), based on mature-equivalent milk yield in the previous lactation. Cows were dried off 45 d before expected calving and randomly assigned to heat stress (HT) or cooling (CL) treatments. Thus, cows received dietary supplementation during late lactation before they were exposed to either CL or HT. After dry-off, treatment groups included heat stress with placebo (HT, only shade, 56 g/d of placebo, n = 17), HT with OG supplementation (HTOG, 56 g/d of OG, n = 19), cooling with placebo (CL, shade, fans, and soakers, 56 g/d of placebo, n = 16), and CL with OG supplementation (CLOG, 56 g/d of OG, n = 11). After parturition, all cows were kept under the same CL system and management, and all cows continued to receive OG or control treatment until 60 DIM. Cooling cows during the dry period reduced afternoon RT (CL vs. HT; 38.9 ± 0.05 vs. 39.3 ± 0.05°C) and RR (CL vs. HT; 45 ± 1.6 vs. 77 ± 1.6 breaths/min). Respiration rate was also decreased by OG supplementation under HT conditions (HTOG vs. HT; 69.7 ± 1.6 vs. 77.2 ± 1.6 breaths/min). An interaction was observed between OG supplementation and HT; HTOG cows tended to have lower morning RT compared with HT cows. During the dry period, OG reduced DMI relative to control cows. Birth weight was greater in calves from CL cows (CL vs. HT; 40.6 ± 1.09 vs. 38.7 ± 1.09 kg). No differences were detected among treatments in hematocrit, total protein, and body condition score. Cows offered CLOG, CL, and HTOG treatments had greater body weight during the dry period (794.9 ± 17.9, 746.8 ± 16.7, and 762.9 ± 14.9 kg, respectively) than HT cows (720 ± 16.2 kg). Gestation length was approximately 4 d longer for CL cows compared with HT cows. Cows offered CLOG, CL, and HTOG treatments produced more milk (41.3 ± 1.6, 40.7 ± 1.6, and 40.5 ± 1.6 kg/d, respectively) than HT treatment (35.9 ± 1.6 kg/d). Body weight after parturition and DMI were evaluated up to 60 DIM and averaged 661.5 ± 15.8 and 19.4 ± 0.7 kg/d, respectively, with no differences observed among treatments. These results confirm that exposure of dry cows to heat stress negatively affects milk yield in the subsequent lactation. Active cooling of dry cows and OG supplementation can reduce the negative effects of heat stress in the dry period on subsequent performance., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Maternal dietary vitamin D carry-over effects were assessed in young pigs to characterise skeletal abnormalities in a diet-induced model of kyphosis. Bone abnormalities were previously induced and bone mineral density (BMD) reduced in offspring from sows fed diets with inadequate vitamin D3. In a nested design, pigs from sows (n 23) fed diets with 0 (-D), 8·125 (+D) or 43·750 (++D) µg D3/kg from breeding through lactation were weaned and, within litter, fed nursery diets arranged as a 2×2 factorial design with 0 (-D) or 7·0 (+D) µg D3/kg, each with 95 % (95P) or 120 % (120P) of P requirements. Selected pigs were euthanised before colostrum consumption at birth (0 weeks, n 23), weaning (3 weeks, n 22) and after a growth period (8 weeks, n 185) for BMD, bone mechanical tests and tissue mRNA analysis. Pigs produced by +D or ++D sows had increased gain at 3 weeks (P<0·05), and at 8 weeks had increased BMD and improved femur mechanical properties. However, responses to nursery diets depended on maternal diets (P<0·05). Relative mRNA expressions of genes revealed a maternal dietary influence at birth in bone osteocalcin and at weaning in kidney 24-hydroxylase (P<0·05). Nursery treatments affected mRNA expressions at 8 weeks. Detection of a maternal and nursery diet interaction (P<0·05) provided insights into the long-term effects of maternal nutritional inputs. Characterising early stages of bone abnormalities provided inferences for humans and animals about maternal dietary influence on offspring skeletal health.

Serotonin regulates numerous processes in the mammary gland. Our objective was to discover novel genes, pathways and functions which serotonin modulates during lactation. The rate limiting enzyme in the synthesis of non-neuronal serotonin is tryptophan-hydroxylase (TPH1). Therefore, we used TPH1 deficient dams (KO; serotonin deficient, n = 4) and compared them to wild-type (WT; n = 4) and rescue (RC; KO + 100 mg/kg 5-hydroxytryptophan injected daily, n = 4) dams. Mammary tissues were collected on day 10 of lactation. Total RNA extraction, amplification, library preparation and sequencing were performed following the Illumina mRNA-Seq. Overall, 97 and 204 genes (false discovery rate, FDR ≤ 0.01) exhibited a minimum of a 2-fold expression difference between WT vs. KO and WT vs. RC dams, respectively. Most differentially expressed genes were related to calcium homeostasis, apoptosis regulation, cell cycle, cell differentiation and proliferation, and the immune response. Additionally, gene set enrichment analysis using Gene Ontology and Medical Subject Headings databases revealed the alteration of several biological processes (FDR ≤ 0.01) including fat cell differentiation and lipid metabolism, regulation of extracellular signal-related kinase and mitogen-activated kinase cascades, insulin resistance, nuclear transport, membrane potential regulation, and calcium release from the endoplasmic reticulum into the cytosol. The majority of the biological processes and pathways altered in the KO dams are central for mammary gland homeostasis. Increasing peripheral serotonin in the RC dams affects specific pathways that favor lactation. Our data confirms the importance of serotonin during lactation in the mammary gland.